Cecchini S, Negrete A, Kotin R M
Laboratory of Biochemical Genetics, NHLBI, National Institutes of Health, Bethesda, MD 20817, USA.
Gene Ther. 2008 Jun;15(11):823-30. doi: 10.1038/gt.2008.61. Epub 2008 Apr 10.
To gain acceptance as a medical treatment, adeno-associated virus (AAV) vectors require a scalable and economical production method. Recent developments indicate that recombinant AAV (rAAV) production in insect cells is compatible with current good manufacturing practice production on an industrial scale. This platform can fully support development of rAAV therapeutics from tissue culture to small animal models, to large animal models, to toxicology studies, to Phase I clinical trials and beyond. Efforts to characterize, optimize and develop insect cell-based rAAV production have culminated in successful bioreactor-scale production of rAAV, with total yields potentially capable of approaching the exa-(10(18)) scale. These advances in large-scale AAV production will allow us to address specific catastrophic, intractable human diseases such as Duchenne muscular dystrophy, for which large amounts of recombinant vector are essential for successful outcome.
为了被认可为一种医学治疗方法，腺相关病毒（AAV）载体需要一种可扩展且经济的生产方法。最近的进展表明，在昆虫细胞中生产重组AAV（rAAV）与当前工业规模的良好生产规范生产是兼容的。该平台可以完全支持rAAV疗法从组织培养到小动物模型、再到大动物模型、毒理学研究、I期临床试验及以后的开发。对基于昆虫细胞的rAAV生产进行表征、优化和开发的努力最终实现了rAAV在生物反应器规模上的成功生产，总产量有可能接近艾可（10¹⁸）规模。大规模AAV生产的这些进展将使我们能够应对特定的灾难性、难治性人类疾病，如杜氏肌营养不良症，对于这种疾病，大量的重组载体对于成功治疗至关重要。
